The Cytotoxic Cell Studies Group has made significant advances in our study of members of the murine Ly49 family. The Ly49 repertoire of 129/J mice was investigated by screening a NK cDNA expression library constructed by our lab. Six novel Ly49 cDNAs have been cloned and characterized. An additional novel Ly49 has been isolated from the CBA/J mouse strain. Three of the new Ly49s we have isolated represent novel NK cell activation receptors (Ly49L, Ly49R and Ly49U). We have shown that these activating receptors associate with the DAP-12 signal transduction molecule that is required for the generation of the activation signal. We are currently investigating the MHC class I specificity of the novel receptors. Our studies of the Ly49 promoter structure have led to the identification of an additional upstream promoter. We have cloned several Ly49 intergenic segments, and a comparison of the promoter regions is underway.